The development of anthrax countermeasures has focused almost exclusively on the perceived threat of inhalational anthrax. However, preparing a sufficiently fine powder of Bacillus anthracis spores for aerosol distribution requires a high degree of technical sophistication. A simple and more credible threat may come from deliberate contamination of food just prior to consumption, so-called "salad bar bioterrorism". Gastrointestinal anthrax, caused by ingestion of B. anthracis spores, can be as deadly as inhalational anthrax and does not respond well to antibiotic treatment, the only therapy currently available. Planet Biotechnology Inc has developed a recombinant immunoadhesin protein, PBI-220, that is remarkably effective at protecting rabbits against inhalational anthrax. PBI-220 is a fusion of CMG2 (the high affinity human anthrax toxin receptor) with human IgG Fc, which we are producing in both transiently and stably transformed plants. In this proposal we wish to develop a rabbit model for gastrointestinal anthrax and determine the efficacy of PBI-220 in that model. In addition we propose to engineer a new immunoadhesin comprised of CMG2 and the Fc of human IgA, co-expressed in plants with human J chain. We plan to use this new immunoadhesin to exploit the natural ability of the body to transport polymeric IgA from the circulation to the lumen of the gut, and in so doing demonstrate another therapy for gastrointestinal anthrax. PUBLIC HEALTH RELEVANCE: The American public is vulnerable to a bioterrorist attack using Anthrax (Bacillus anthracis). We believe than an immunoadhesin, comprised of the human anthrax toxin receptor CMG2 and a human IgG or IgA Fc, can provide complete protection against anthrax after the development of symptoms, without the need for vaccination, and would allow the development of the body's own protective antibodies against Bacillus anthracis.